Two-Stage Distance Feature-based Optimization Algorithm for De novo Protein Structure Prediction.

De novo protein structure prediction can be treated as a conformational space optimization problem under the guidance of an energy function. However, it is a challenge of how to design an accurate energy function which ensures low-energy conformations close to native structures. Fortunately, recent studies have shown that the accuracy of de novo protein structure prediction can be significantly improved by integrating the residue-residue distance information. In this paper, a two-stage distance feature-based optimization algorithm (TDFO) for de novo protein structure prediction is proposed within the framework of evolutionary algorithm. In TDFO, a similarity model is first designed by using feature information which is extracted from distance profiles by bisecting K-means algorithm. The similarity model-based selection strategy is then developed to guide conformation search, and thus improve the quality of the predicted models. Moreover, global and local mutation strategies are designed, and a state estimation strategy is also proposed to strike a trade-off between the exploration and exploitation of the search space. Experimental results of 35 benchmark proteins show that the proposed TDFO can improve prediction accuracy for a large portion of test proteins.

Secondary Structure and Contact Guided Differential Evolution for Protein Structure Prediction.

Ab initio protein tertiary structure prediction is one of the long-standing problems in structural bioinformatics. With the help of residue-residue contact and secondary structure prediction information, the accuracy of ab initio structure prediction can be enhanced. In this study, an improved differential evolution with secondary structure and residue-residue contact information referred to as SCDE is proposed for protein structure prediction. In SCDE, two score models based on secondary structure and contact information are proposed, and two selection strategies, namely, secondary structure-based selection strategy and contact-based selection strategy, are designed to guide conformation space search. A probability distribution function is designed to balance these two selection strategies. Experimental results on a benchmark dataset with 28 proteins and four free model targets in CASP12 demonstrate that the proposed SCDE is effective and efficient.

Loop Enhanced Conformational Resampling Method for Protein Structure Prediction.

Protein structure prediction has been a long-standing problem for the past decades. In particular, the loop region structure remains an obstacle in forming an accurate protein tertiary structure because of its flexibility. In this study, Rama torsion angle and secondary structure feature-guided differential evolution named RSDE is proposed to predict three-dimensional structure with the exploitation on the loop region structure. In RSDE, the structure of the loop region is improved by the following: loop-based cross operator, which interchanges configuration of a randomly selected loop region between individuals, and loop-based mutate operator, which considers torsion angle feature into conformational sampling. A stochastic ranking selective strategy is designed to select conformations with low energy and near-native structure. Moreover, the conformational resampling method, which uses previously learned knowledge to guide subsequent sampling, is proposed to improve the sampling efficiency. Experiments on a total of 28 test proteins reveals that the proposed RSDE is effective and can obtain native-like models.